Embryonic microglia, when first colonizing the nervous system, do not display the extensively ramified morphology observed in the adult CNS, instead adopting an amoeboid morphology as they migrate and spread through the parenchyma. Likewise, pMGLs progressively adopt a ramified morphology when cultured in isolation, as they lose their proliferation potential. In isolation, their morphology and function can be analyzed for cell-autonomous phenotypes. We showed that MECP2 mutant microglia are smaller than their isogenic counterpart: this may contribute to functional differences in Rett microglia worthy of further investigation.